While serological tests work well for several other infectious diseases, antibody tests for TB are increasingly recognised to be inaccurate, inconsistent and of no clinical value.

But although most regulatory and guidance bodies have mechanisms in place to withdraw or ban ineffective or dangerous drugs and vaccines, there is little awareness of the consequences of poor diagnostic tests, and few safeguards in place to stop their use.

Yet misdiagnosis of TB can be harmful both to patients and to public health. For patients, it may include financial loss, unnecessary therapy (after false-positive results), or morbidity and mortality after false-negative tests fail to pick up the disease. From a public health perspective, every missed TB diagnosis may result in additional transmission.

But the WHO can only make recommendations. It is now up to governments to act.

Commercial antibody testing is widespread

Until recently, the TB community was not aware of the magnitude of the use and therefore the potential misuse of serological tests. Now the picture is becoming clearer, in India at least.

Research by my team at McGill University has estimated that at least 1.5 million TB serological tests are done in the country every year, at a cost conservatively estimated at US$15 million.

The problem is not confined to India. Commercial serological tests are available in at least 17 of 22 countries with the highest burden of TB, including China, South Africa, Brazil, Indonesia, Nigeria, Kenya, Uganda, Afghanistan, Myanmar, Pakistan, the Russian Federation and the Philippines.

Regulation of diagnostics is weak in these countries, with the result that poorly performing tests can easily enter the market. Once there, the money to be made by stakeholders doctors, laboratories, diagnostic companies and distributors ensures that they are widely used, even without any policy or scientific evidence supporting such use.

A substandard test

Last year, the WHO finally decided to tackle this problem and convened an expert group to review the evidence and formulate a policy.

An updated meta-analysis, commissioned by TDR (Special Programme for Research and Training in Tropical Diseases) and WHO, and published in PLoS Medicine this month (9 August), has brought together evidence from 92 studies[1].

It concludes that commercial serological tests continue to produce inconsistent and imprecise estimates of sensitivity and specificity, and that the quality of evidence supporting their effectiveness remains very low.

The expert group also considered evidence from a study of the cost-effectiveness of the use of serological tests in India[2].

This study found that, as an initial test for active TB among adults in the country, serology results in more human suffering, secondary infections and false-positive diagnoses than the more conventional sputum-smear microscopy tests, while also increasing costs per patient to the Indian TB control sector.

Last month's statement issued by WHO, which is based on these two studies and additional advice from experts, concludes that the quality of evidence for commercial serodiagnostic tests was very low, with harms/risks far outweighing any potential benefits .

It therefore recommends that these tests should not be used in individuals suspected of active pulmonary or extra-pulmonary TB, irrespective of their HIV status, although the WHO policy does not discourage research to develop improved or novel serological tests for TB.

Influencing the private sector

But while the WHO statement criticising serological TB testing [292kB] provides much needed guidance at the global level on what needs to be done, the agency does not have the power to implement policy that would put its conclusions into effect.

It is now up to high-burden countries to implement the policy by tightening their regulations, and by educating doctors, laboratories and consumers on the need to prevent the continued misuse of such diagnostics.

The big challenge is to reach and influence the private sector, which is largely unregulated in most developing countries. In India, for example, the private sector manages nearly half of all TB cases, and irrational medical practices such as those involved in TB drug use are rampant.

India has already taken a lead. Immediately following the WHO policy announcement, India's Revised National TB Control Program (RNTCP) issued an advisory against TB serological tests, but this may not directly influence practices in the private sector.

Political will is needed

Other countries with a high burden of TB, such as South Africa, Brazil, Indonesia, Pakistan, Bangladesh, Philippines, Kenya and Nigeria, need to follow India's example. Each also has a strong private sector, but must find ways to incentivise it to substitute serological tests with validated products endorsed by WHO.

If diagnostic companies, distributors, laboratories and doctors can earn money from suboptimal tests, then their use will continue to flourish, however dubious the results. A solution must account for these market-based ground realities, and address the financial incentives of all stakeholders that currently perpetuate bad medicine.

There is plenty of scope for creative public-private partnerships that can realign irrational medical practices with evidence-based guidelines, yet still be economically viable for private providers and companies.

What is needed is the political will to ensure that such solutions are put into place and to overcome the entrenched resistance they will inevitably face.

Madhukar Pai is an associate professor of epidemiology at McGill University, Montreal and McGill University Health Centre. He co-chairs the Stop TB Partnership's New Diagnostics Working Group, and consults for the Bill Melinda Gates Foundation. The views expressed in this article are those of the author and may not reflect those held by the agencies he works with.